Interaction of angiotensin with disseminated intravascular coagulation: a possible mechanism in the genesis of acute renal failure.

Because of the importance of the renin-angiotensin system in renal homeostatic mechanisms, the effect of angiotensin administration upon disseminated intravascular coagulation has been studied in rabbits. An infusion of angiotensin II (0.1 mug/kg/min for 2 hours) produced neither histologic abnormalities in the kidneys nor an elevation of creatinine. After an infusion of thrombin (2.0 units/kg/min for 2 hours) only 3 of 10 rabbits, when sacrified 24 hours later, showed histologic lesions comprised of occasional fibrin thrombi and foci of tubular necrosis. Creatinine levels did not rise. In contrast, the combination of angiotensin and thrombin resulted in renal lesions in 12 of 14 animals. Four had frank cortical necrosis, while combinations of tubular necrosis, glomerular thrombosis and segmental glomerular infarction occurred in the others, together with elevated creatinine levels. Blockade of alpha-adrenoreceptors with phenoxybenzamine in 12 animals did not prevent either these histologic changes or creatinine elevation, showing that the effect of angiotensin was independent of alpha-adrenoreceptor stimulation. The synergistic interaction between angiotensin and disseminated intravascular coagulation was not explained by differences in the consumption of plasma fibrinogen but apparently was due to localization of fibrin thrombi within glomerular capillaries by the vasomotor actions of angiotensin, as has previously been shown to occur with alpha-adrenoreceptor simulation. Such a mechanism might contribute to renal glomerular deposition of fibrin in acute ischemic renal failure.